Classification and regression tree for estimating predictive markers to detect T790M mutations after acquired resistance to first line EGFR-TKI: HOPE-002.

BACKGROUND AND OBJECTIVE: Osimertinib as first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor (EGFR) mutations remains controversial. Sequential EGFR-tyrosine kinase inhibitor (TKI) might be superior to the first line osimertinib in patients at risk of developing acquired T790M mutations. METHODS: We enrolled consecutive patients with EGFR-mutated (deletion 19 or L858R) advanced NSCLC treated with first-line drugs and evaluated predictive markers using classification and regression tree (CART) for the detection of T790M mutations based on patient backgrounds prior to initial treatment. RESULTS: Patients without acquired T790M mutations had worse outcomes than those with T790M mutations (median OS: 798 days vs. not reached; HR: 2.70; P < 0.001). CART identified three distinct groups based on variables associated with acquired T790M mutations (age, CYF, WBC, liver metastasis, and LDH; AUROC: 0.77). Based on certain variables, CART identified three distinct groups in deletion 19 (albumin, LDH, bone metastasis, pleural effusion, and WBC; AUROC: 0.81) and two distinct groups in L858R (age, CEA, and ALP; AUROC: 0.80). The T790M detection frequencies after TKI resistance of afatinib and first-generation EGFR-TKIs were similar (35.3% vs. 37.4%, P = 0.933). Afatinib demonstrated longer PFS (398 vs. 279 days; HR: 0.67; P = 0.004) and OS (1053 vs. 956 days; HR: 0.68; P = 0.051) than first-generation EGFR-TKIs. CONCLUSION: Identification of patients at risk of acquiring T790M mutations after EGFR-TKI failure may aid in choice of first-line EGFR-TKI. Furthermore, afatinib may be the more effective 1st-line EGFR-TKI treatment for patients at risk of developing T790M as initial EGFR-TKI resistance.

Comparison of gemcitabine plus nab-paclitaxel and FOLFIRINOX in metastatic pancreatic cancer.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GA) and modified FOLFIRINOX (FFX) have been widely used as standard first-line treatment in pancreatic cancer. However, it is unclear which regimen is more efficacious. AIM: To evaluate a retrospective analysis comparing the efficacy and safety of FFX and GA as first-line chemotherapeutic regimens in patients with metastatic pancreatic cancer. METHODS: We retrospectively analyzed and compared outcomes in 101 patients who presented with pancreatic cancer and were treated with either GA (n = 54) or FFX (n = 47). Moreover, we performed subgroup analysis based on the neutrophil/lymphocyte ratio (NLR) and Eastern Cooperative Oncology Group (ECOG) performance status. RESULTS: There were no significant differences between two groups in baseline characteristics, except for the ECOG performance status. The median progression-free survival (PFS) (6.43 mo vs 4.90 mo, P = 0.058) was comparable between two groups; however, median overall survival (OS) (10.17 mo vs 6.93 mo, P = 0.008) was longer in patients who received GA regimen. In patients with ECOG 0 (PFS: 8.93 mo vs 5.43 mo, P = 0.002; OS: 16.10 mo vs 6.97 mo, P = 0.000) and those with NLR < 3 (PFS: 8.10 mo vs 6.57 mo, P = 0.008; OS: 12.87 mo vs 9.93 mo, P = 0.002), GA regimen showed higher efficacy. CONCLUSION: GA regimen may be recommended to the patients with NLR < 3 or ECOG 0 status although GA and FFX showed comparable efficacy outcomes in patients with metastatic pancreatic cancer.

Is rifampin resistance a reliable predictive marker of multidrug-resistant tuberculosis in China: A meta-analysis of findings.

OBJECTIVES: Systematic review of multidrug-resistant tuberculosis (MDR-TB) prevalence among rifampicin (RIF)-resistant tuberculosis (RR-TB) patients in 34 provinces of China was conducted to correlate RIF resistance with concurrent isoniazid (INH) resistance. METHODS: Database searches (PubMed, Embase, China National Knowledge Infrastructure, Chinese Scientific Journal, Wanfang), identified drug resistance surveillance studies conducted between January 1, 2000 and June 30, 2018. Of 1554 records, random-effects meta-analysis of 34 studies of adequate methodological quality yielded 108,366 TB cases for MDR-TB prevalence analysis of RR-TB cases. RESULTS: MDR-TB prevalence among RR-TB cases varied from 57% (Xinjiang; 95% CI 47%, 67%) to 95% (Taiwan; 95% CI 92%, 98%), for a pooled national rate of 77% (95% CI 75%, 80%). Subgroup and meta-regression analyses revealed greater MDR-TB prevalence in previously treated versus new RR-TB cases (P < 0.001), with no significant differences of regional initial drug resistance rates or sampling methods. Regional MDR-TB prevalence among RR-TB cases was lowest (69%) in the Northeast Region (95% CI 65%, 73%) and highest (90%) in Hong Kong, Macao and Taiwan (95% CI 81%, 98%). CONCLUSIONS: In China, ∼77% of RR-TB cases are MDR-TB. Thus, RIF resistance cannot effectively predict MDR-TB. Highly variable RR-TB prevalence across China warrants improved TB management.